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Chlamydial Histones Control Developmental Fitness in the Next Infection Cycle.

Yuxuan Wang1, Matthew Pan1, Temitope V Coker1

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Chlamydial histones HctA and HctB are crucial for bacterial development. Their deficiency during elementary body maturation impairs the next infection cycle, affecting differentiation and growth.

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Area of Science:

  • Microbiology
  • Bacterial genetics
  • Cell biology

Background:

  • Chlamydia trachomatis undergoes a complex developmental cycle involving elementary bodies (EBs) and reticulate bodies (RBs).
  • Chlamydial histones HctA and HctB are implicated in chromosome remodeling during the differentiation of RBs into infectious EBs.
  • These bacterial histones share homology with mammalian histones and are developmentally regulated.

Purpose of the Study:

  • To investigate the role of chlamydial histones HctA and HctB in the developmental cycle of Chlamydia trachomatis.
  • To determine the impact of histone deficiency on EB production, nucleoid condensation, and subsequent infection cycles.

Main Methods:

  • Utilized an inducible CRISPR interference system to repress the expression of hctA, hctB, or both genes in Chlamydia trachomatis.
  • Assessed EB yield, nucleoid condensation, genome replication onset, and genome accumulation in secondary infection cycles initiated with EBs derived from histone-repressed cultures.

Main Results:

  • Repression of hctA, hctB, or both genes individually resulted in modest reductions in EB yield and did not prevent nucleoid condensation during the parental cycle.
  • Histone deficiency during EB maturation significantly impaired the fitness of progeny EBs in the subsequent infection cycle.
  • HctA deficiency led to delayed genome replication, while combined hctA and hctB repression caused delayed replication and reduced genome accumulation, indicating defects in RB formation and growth.

Conclusions:

  • Chlamydial histones HctA and HctB play a critical transgenerational role in maintaining bacterial developmental fitness.
  • Chromosome organization during EB maturation, influenced by HctA and HctB, is essential for efficient primary EB-to-RB differentiation and RB growth in the next infection cycle.
  • Partial functional redundancy exists between HctA and HctB, and other factors likely contribute to EB chromosome compaction.